Low Mitotic Activity in Papillary Thyroid Cancer: A Marker for Aggressive Features and Recurrence

Context: The significance of low mitotic activity in papillary thyroid cancer (PTC) is largely undefined. Objective We aimed to determine the behavioral landscape of PTC with low mitotic activity compared with that of no and high mitotic activity. Methods: A single-institution consecutive series of patients with PTC from 2018 to 2022 was reviewed. Mitotic activity was defined as no mitoses, low (1-2 mitoses/2 mm2) or high (>= 3 mitoses/2 mm2) per the World Health Organization. The 2015 American Thyroid Association risk stratification was applied to the cohort, and clinicopathologic features were compared between groups. For patients with >= 6 months of follow-up, Cox regression analyses for recurrence were performed. Results: A total of 640 PTCs were included-515 (80.5%) no mitotic activity, 110 (17.2%) low mitotic activity, and 15 (2.3%) high mitotic activity. Overall, low mitotic activity exhibited rates of clinicopathologic features including vascular invasion, gross extrathyroidal extension, and lymph node metastases in between those of no and high mitotic activity. PTCs with low mitotic activity had higher rates of intermediate- and high-risk American Thyroid Association (ATA) risk stratification compared with those with no mitotic activity (P < .001). Low mitotic activity PTCs also had higher recurrence rates (15.5% vs 4.5%, P < .001). Low mitotic activity was associated with recurrence, independent of the ATA risk stratification (HR 2.96; 95% CI 1.28-6.87, P = .01). Conclusion: Low mitotic activity is relatively common in PTC and its behavior lies within a spectrum between no and high mitotic activity. Given its association with aggressive clinicopathologic features and recurrence, low mitotic activity should be considered when risk stratifying patients with PTC for recurrence.